GP9 p.Ala141=
c.423G>A · rs553559631 · VCV900154
ClinGen expert panel — Platelet Disorders VCEP
Likely Benign for Bernard-Soulier syndrome. Applied ACMG criteria (verbatim):
BP7 BP4
Curation rationale (ClinGen, verbatim)
The c.423G>A variant is a synonymous (silent) variant (p.Ala141=) that is not predicted by SpliceAI to impact splicing (score <0.2, BP4). In addition, it occurs at a nucleotide that is not highly conserved as shown by phyloP score of -1.8 (<1.5) (BP7). The Grpmax Filtering allele frequency in gnomAD v4.1 is 0.0001647 (based on 216/1167496alleles) in the European (non-Finnish) population, which is above the ClinGen PD VCEP PM2_supporting threshold (<0.0000329) but below the BS1 threshold (>0.0007). In summary, this variant meets the criteria to be classified as likely benign for autosomal recessive Bernard-Soulier syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: BP4, BP7
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.6 | GERP -4 |
| Overall | ||
| CADD | 0.616 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0185% | 5,405 |
| Middle Eastern | 0.0176% | 5,666 |
| Remaining individualsnot grpmax-eligible | 0.0163% | 6,130 |
| Admixed American | 0.0107% | 9,314 |
| South Asian | 0.00794% | 12,589 |
| East Asian | 0.00693% | 14,429 |
| African / African-American | 0.00403% | 24,803 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- GP9
- Protein
- p.Ala141=
- Coding
- c.423G>A
- MANE Select
- NM_000174
- dbSNP
- rs553559631
- Type
- single nucleotide variant
- Location
- chr3:129062162 (GRCh38)
- Structure
- AlphaFold pLDDT 84.43 · 2 PDB
Disease context
Bernard-Soulier syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Bernard-Soulier syndrome (Orphanet):
- Inheritance
- Autosomal dominant, Autosomal recessive
- Onset
- All ages
Similar variants
- GP9 p.Ala141Val Uncertain significance ★ ⚠ same residue
- GP9 p.Asn61Ser Pathogenic ★★★ same condition
- GP9 p.Cys135Tyr Likely pathogenic ★★★ ⚠ same condition
- GP9 p.Cys24Arg Likely pathogenic ★★★ same condition
- GP9 p.Cys38Arg Likely pathogenic ★★★ same condition
- GP9 p.Cys89Tyr Pathogenic ★★★ same condition
- GP9 p.Leu56Pro Likely pathogenic ★★★ same condition
- GP9 p.Leu7Pro Likely pathogenic ★★★ ⚠ same condition
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/gp9-p-ala141 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown